Search

Objective: Dyspnea, or breathlessness, is an important symptom in amyotrophic lateral sclerosis/motor neuron disease (ALS/MND). We examined the measurement properties of the Dyspnea-12., Methods: Rasch analysis enabled conversion of raw Dyspnea-12 scores to interval level metric equivalents. Converted data were used to perform trajectory modeling; those following different trajectories were compared for demographic, clinical, symptom, and functioning characteristics. Logistic regression examined differences between distinct trajectories., Results: In 1022 people, at baseline, mean metric Dyspnea-12 was 7.6 (SD 9.3). 49.8% had dyspnea, severe in 12.6%. Trajectory analysis over 28 months revealed three breathlessness trajectories: group 1 reported none at baseline/follow-up (42.7%); group 2 significantly increased over time (9.4%); group 3 had a much higher level at baseline which rose over follow-up (47.9%). Group 3 had worse outcomes on all symptoms, functioning and quality of life; compared to group 1, their odds of: respiratory onset sixfold greater; King's stage ≥3 2.9 greater; increased odds of being bothered by choking, head drop, fasciculations, and muscle cramps; fatigue and anxiety also elevated ( p  < .01)., Conclusion: Dyspnea is a cardinal symptom in ALS/MND and can be quickly measured using the Dyspnea-12. Raw scores can easily be converted to interval level measurement, for valid change scores and trajectory modeling. Dyspnea trajectories reveal different patterns, showing that clinical services must provide monitoring which is customized to individual patient need. Almost half of this large population had worsening dyspnea, confirming the importance of respiratory monitoring and interventions being integrated into routine ALS care.

Aim: To evaluate the impact of usual care plus a fundamental nursing care guideline compared to usual care only for patients in hospital with COVID-19 on patient experience, care quality, functional ability, treatment outcomes, nurses' moral distress, patient health-related quality of life and cost-effectiveness., Design: Parallel two-arm, cluster-level randomized controlled trial., Methods: Between 18th January and 20th December 2021, we recruited (i) adults aged 18 years and over with COVID-19, excluding those invasively ventilated, admitted for at least three days or nights in UK Hospital Trusts; (ii) nurses caring for them. We randomly assigned hospitals to use a fundamental nursing care guideline and usual care or usual care only. Our patient-reported co-primary outcomes were the Relational Aspects of Care Questionnaire and four scales from the Quality from the Patient Perspective Questionnaire. We undertook intention-to-treat analyses., Results: We randomized 15 clusters and recruited 581 patient and 418 nurse participants. Primary outcome data were available for 570-572 (98.1%-98.5%) patient participants in 14 clusters. We found no evidence of between-group differences on any patient, nurse or economic outcomes. We found between-group differences over time, in favour of the intervention, for three of our five co-primary outcomes, and a significant interaction on one primary patient outcome for ethnicity (white British vs. other) and allocated group in favour of the intervention for the 'other' ethnicity subgroup., Conclusion: We did not detect an overall difference in patient experience for a fundamental nursing care guideline compared to usual care. We have indications the guideline may have aided sustaining good practice over time and had a more positive impact on non-white British patients' experience of care., Implications for the Profession And/or Patient Care: We cannot recommend the wholescale implementation of our guideline into routine nursing practice. Further intervention development, feasibility, pilot and evaluation studies are required., Impact: Fundamental nursing care drives patient experience but is severely impacted in pandemics. Our guideline was not superior to usual care, albeit it may sustain good practice and have a positive impact on non-white British patients' experience of care., Reporting Method: CONSORT and CONSERVE., Patient or Public Contribution: Patients with experience of hospitalization with COVID-19 were involved in guideline development and writing, trial management and interpretation of findings., (© 2023 The Authors. Journal of Advanced Nursing published by John Wiley & Sons Ltd.)

Purpose: Social media (SoMe) is increasingly important in surgical education and may be necessary in the current learning environment. Whilst expanding in use and applications, few studies detail the impact of SoMe on measurable outcomes. The goal of this study was to quantify the impact of a dedicated SoMe strategy on engagement metrics for surgical research., Methods: A retrospective review of a peer-reviewed surgical journal's Twitter microblog platform (@ColorectalDis) was performed from 6/2015 to 4/2021. A formal SoMe strategy was introduced in September 2018. Data were stratified into 2 time periods: pre-intervention (6-2015 to 9-2018) and post-SoMe intervention (9-2018 to 4-2021). The main outcome was the impact of the SoMe strategy on user engagement with the Twitter platform, journal, and traditional journal metrics. Twitter Analytics and Twitonomy were used to analyse engagement., Results: From conception to analysis, the microblog published 1198 original tweets, generating 5 million impressions and 231,000 engagements. Increased account activity (increased tweets published per month-5.51 vs 28.79; p < 0.01) was associated with significant engagement growth, including new monthly followers (213 vs 38; p < 0.01) and interactions with posted articles (4,096,167 vs 269,152; p < 0.01). Article downloads increased twenty-fold post-SoMe intervention (210,449 vs 10,934; p < 0.01), with significant increases in traditional journal metrics of new subscribers (+11%), article submissions (+24%), and impact factor (+0.9) (all p < 0.01)., Conclusion: SoMe directly impacts traditional journal metrics in surgical research. By examining the patterns of user engagement between SoMe and journal sites, the growing beneficial impact of a structured social media strategy and SoMe as an educational tool is demonstrated., (© 2023. The Author(s).)

Background: Suprascapular nerve blockade (SSNB) through injection (SSNBi) and/or pulsed radiofrequency (PRF) provide options for the management of painful shoulder pathology. Multiple techniques for delivery of SSNB are described but no consensus on optimal symptom control is available. This systematic review and meta-analysis aims to assess patient-focussed outcomes in SSNB and explore the impact of variation in the technical application of this treatment modality., Methods: MEDLINE, Embase and CINAHL were searched for case series, cohort studies and randomised control trials published from database inception until 28 January 2021. Articles reporting use of SSNBi or PRF for treatment of shoulder pain with a minimum 3 months follow-up were included. Patient-reported outcome measures (PROMs) were extracted and the pooled standardised mean difference (SMD), weighted by study size, was reported. Quality of methodology was assessed using Wylde's nonsummative four-point system., Findings: Of 758 references, 18 studies were included, totalling 704 SSNB. Average pain improvement at 3 months was 52.3%, with meta-analysis demonstrating a SMD of 2.37. Whereas SSNBi combined with PRF shows the greatest SMD of 2.75, this did not differ significantly from SSNBi or PRF when used as monotherapy. Location of treatment and the guidance technique used did not influence outcome., Conclusion: SSNBi and PRF provide safe and effective treatment for shoulder pain, as judged by PROMs. This may be of particular value in aging or comorbid patients and with surgical restrictions during the COVID-19 pandemic. Regardless of technique, patients experience a marked improvement in pain that is maintained beyond 3 months.

Aims: To assess the real-world evidence for flash glucose monitoring (Abbott FreeStyle Libre) for children with type 1 diabetes in terms of glucose control, secondary healthcare resources and costs., Research Design and Methods: We conducted a controlled before and after study (approximately 12 months before and after) using routinely collected health record data on children who start using flash monitors and a control population of children with self-monitoring of blood glucose (SMBG). Our population-based sample of eligible individuals using flash monitoring (n=114) and controls (n=80) aged between 4 and 18 years was drawn from four paediatric diabetes clinics (secondary care) in the South West England. Outcome measures included: glycated hemoglobin (HbA1c), frequency of BG tests; frequency of sensor scans; time in recommended glucose range; short-term complications (hypoglycemia, diabetic ketoacidosis and related illness resulting in investigation) and secondary care costs., Results: After adjustment for age, time since diagnosis, deprivation and the test modality (point of care or laboratory), the mean HbA1c reading for controls was 61.2 (mmol/mol) for the period before and 63.9 after. For individuals using flash monitoring, the adjusted mean HbA1c reading was 64.6 for the period before implementation and 63.8 after. Rates of short-term complications were low across all groups in the study. Whereas the 'after' flash monitoring group had substantially higher incremental costs (+£703 vs the flash monitoring 'before' comparison and +£841 vs contemporaneous SMBG controls), these cost differences were driven by primary care prescribing (sensor costs)., Conclusions: There was some indication that flash monitoring might help young people improve the control of their diabetes but for our sample, the difference between finger-prick testing and flash monitoring was not clinically significant (HbA1c improvement <5 mmol/mol). Given the pace of technological change within diabetes, research efforts should now facilitate the real-time analysis of long-term routine data on flash and continuous glucose monitors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

The United Kingdom is recognised worldwide as a leader in genomics. The use of genomic technologies in the National Health Service (NHS) is expected to deliver faster and more accurate diagnoses, supporting personalized treatments to improve patient outcomes. The ambition of embedding genomic medicine in the diagnostic pathway requires involvement of the front-line clinical workforce, known as 'mainstreaming'. Nurses and midwives are the largest professionally qualified workforce in the National Health Service thus, it is anticipated that they will play key roles in mainstreaming. This study investigated the level of competence/confidence of practicing nurses and midwives to support mainstreaming and their perception of the importance of genomics in delivery of patient care. A literature review of genetics/genomics competency frameworks, semi structured interviews of lead nurses and stakeholders were conducted to identify relevant competencies needed for mainstreaming. These were then used to survey four cohorts of nurses ( n = 153) across England in four consecutive years (2019-22). The confidence level of these professionals in all aspects of genomics was 2.07 ± 0.47 measured on a 5-point Likert scale (1" Low confidence "; 5 " High confidence "). Intriguingly, these professionals all appreciated the importance of genomics for their patient care (4.01 ± 0.06). Whilst the importance scores increased, the confidence scores declined at the time when major genomic transformation took place in the NHS (e.g.: launch of the Genomic Medicine Service, the National Genomic Test Directory). To bridge this gap, relevant genomic education can play key roles. However, nurses and midwives were found to be grossly underrepresented in formal genomic education courses offered by Health Education England Genomics Education Programme since 2014. This may result from the lack of direct applicability of the currently offered courses for their practice and role. Thematic analysis revealed that nurses and midwives wish to support their patients by providing more information on their condition, inheritance, and treatment options in combination with the use of relevant genetic counselling skills. This study identified easy to follow competencies for embedding genomics into routine clinical care. We propose a training programme that addresses the gap that nurses and midwives currently have, to enable them to harness genomic opportunities for patients and services., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Carpenter-Clawson, Watson, Pope, Lynch, Miles, Bell, Talbot and Varadi.)

Aims: Arthroplasty is being increasingly used for the management of distal humeral fractures (DHFs) in elderly patients. Arthroplasty options include total elbow arthroplasty (TEA) and hemiarthroplasty (HA); both have unique complications and there is not yet a consensus on which implant is superior. This systematic review asked: in patients aged over 65 years with unreconstructable DHFs, what differences are there in outcomes, as measured by patient-reported outcome measures (PROMs), range of motion (ROM), and complications, between distal humeral HA and TEA?, Methods: A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on PROMs, ROM, and complications. PROMs and ROM results were reported descriptively and a meta-analysis of complications was conducted. Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROSPERO (CRD42021228329)., Results: A total of 29 studies met the inclusion and exclusion criteria. The mean Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) score was 19.6 (SD 7.5) for HA and 38 (SD 11.9) for TEA and the mean abbreviated version of DASH was 17.2 (SD 13.2) for HA and 24.9 (SD 4.8) for TEA. The Mayo Elbow Performance Score was the most commonly reported PROM across included studies, with a mean of 87 (SD 5.3) in HA and 88.3 (SD 5) in TEA. High complication rates were seen in both HA (22% (95% confidence interval (CI) 5 to 44)) and TEA (21% (95% CI 13 to 30), but no statistically significant difference identified., Conclusion: This systematic review has indicated PROMs and ROM mostly favouring HA, but with a similarly high complication rate in the two procedures. However, due to the small sample size and heterogeneity between studies, strength of evidence for these findings is low. We propose further research in the form of a national randomized controlled trial. Cite this article: Bone Joint J  2022;104-B(5):559-566.

Aim: To establish if detailed review of trauma reports with reference to coding manual improved accuracy of ISS and to establish if demonstrated changes in coding affected performance and tariff payment., Materials and Methods: A study was undertaken which gathered data from 6 months across the five trusts with information on imaging undertaken, mechanism of injury (MOI), Injury Severity Score (ISS), and injury descriptors was included. Patients with ISS near to a best practice tariff boundary of 9 and 16 (5-8 and 11-15) then had their imaging reviewed by the Radiology Department with direct reference to the ISS coding manual. Injuries were then re-coded and ISS recalculated., Results: Over the 6-month period, 1,693 patients were admitted to the database from the five hospitals. One hundred and sixty-nine (9.9%) patients met the inclusion criteria for review. Thirty-five (20.7%) had a change in abbreviated (region specific) injury code, with 30 a change in the resultant ISS. Three had a decrease in ISS and 27 increased ISS with all 27 moving across an ISS best practice tariff and three moving across two payment tariff boundaries. With re-coding, there was a potential £15,000 of lost revenue from the major trauma centre (MTC) alone., Conclusion: Reporting with reference to ISS description improves the accuracy of ISS significantly. Radiologists improving the descriptions of specific injury patterns and adopting 'Trauma Audit and Research Network friendly' reporting strategies may improve data accuracy, performance, and payment of best practice tariffs to hospitals., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)

Objective: To conduct a systematic review of the clinical literature to determine whether ultrasound can be used to improve the reduction of distal radius fractures in adults in the ED., Methodology: A study protocol was registered on PROSPERO. EMBASE, PubMed/MEDLINE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov of the US National Library of Medicine were searched for studies evaluating ultrasound-assisted distal radial fracture reductions in comparison with standard care. The primary outcome of interest was manipulation success rates, defined as the proportion of fracture manipulations resulting in acceptable anatomical alignment, with secondary outcome being subsequent surgical intervention rates in ultrasound and standard care group of patients., Results: 248 were screened at title and abstract, and 10 studies were included for a narrative synthesis. The quality of this evidence is limited but suggests ultrasound is accurate in determining distal radius fracture reduction and may improve the quality of reduction compared with standard care. However, there is insufficient evidence to determine whether this affects the rate of subsequent surgical intervention or functional outcome., Conclusion: There is a lack of evidence that using ultrasound in the closed reduction of distal radius fractures benefits patients. Properly conducted randomised controlled trials with patient-orientated outcomes are crucial to investigate this technology., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: The 100 000 Genomes Project was completed in 2019 with the objective of integrating genomic medicine into routine National Health Service (NHS) clinical pathways. This project and genomic research will revolutionize the way we practice colorectal surgery in the 21st century. This paper aims to provide an overview of genomic medicine and its implications for the colorectal surgeon., Results: Within NHS England, consolidation has created seven regional Genomic Laboratory Hubs. DNA from solid tumours, including colorectal cancers, will be assessed using 500-gene panels, results will be fed back to Genome Tumour Advisory Boards. Identifying variants from biopsies earlier in the clinical pathway may alter surgical and other treatment options for patients. However, there is an important distinction between somatic variants within a tumour biopsy and germline variants that may suggest a heritable condition such as Lynch syndrome. Novel drugs, for example immunotherapy, will increase treatment options including downstaging cancers and changing the surgical approach. The use of circulating tumour DNA (liquid biopsies) will have applications in diagnosis, treatment and surveillance of cancer. There are many exciting potential future applications of this technology for offering personalized medicine that will require multidisciplinary working and the colorectal community., Conclusion: There are many challenges but also exciting opportunities to embed new 'omic' technologies and innovation into 21st century colorectal surgery. The next phase for the colorectal community is how we engage with this change, with questions around training, identification of genomic multidisciplinary team (MDT) champions and how we collaborate with the core members of the MDT, clinical geneticists and national genomic testing., (© 2021 The Association of Coloproctology of Great Britain and Ireland.)

Aims: This systematic review asked which patterns of complications are associated with the three reverse total shoulder arthroplasty (RTSA) prosthetic designs, as classified by Routman et al, in patients undergoing RTSA for the management of cuff tear arthropathy, massive cuff tear, osteoarthritis, and rheumatoid arthritis. The three implant design philosophies investigated were medial glenoid/medial humerus (MGMH), medial glenoid/lateral humerus (MGLH), and lateral glenoid/medial humerus (LGMH)., Methods: A systematic review of the literature was performed via a search of MEDLINE and Embase. Two reviewers extracted data on complication occurrence and patient-reported outcome measures (PROMs). Meta-analysis was conducted on the reported proportion of complications, weighted by sample size, and PROMs were pooled using the reported standardized mean difference (SMD). Quality of methodology was assessed using Wylde's non-summative four-point system. The study was registered with PROSPERO (CRD42020193041)., Results: A total of 42 studies met the inclusion and exclusion criteria. Rates of scapular notching were found to be significantly higher in MGMH implants (52% (95% confidence interval (CI) 40 to 63)) compared with MGLH ((18% (95% CI 6 to 34)) and LGMH (12% (95% CI 3 to 26)). Higher rates of glenoid loosening were seen in MGMH implants (6% (95% CI 3 to 10)) than in MGLH implants (0% (95% CI 0 to 2)). However, strength of evidence for this finding was low. No significant differences were identified in any other complication, and there were no significant differences observed in PROMs between implant philosophies., Conclusion: This systematic review has found significant improvement in PROMS and low complication rates across the implant philosophies studied. Scapular notching was the only complication found definitely to have significantly higher prevalence with the MGMH implant design. Cite this article: Bone Joint J  2021;103-B(5):813-821.

Introduction: With the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic., Materials and Methods: A protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 'clean' site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff., Results: A total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive., Conclusion: This study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery.

Objective: The progressively disabling and terminal nature of ALS/MND imposes major coping demands on patients. We wished to improve the psychometric properties of our previously published MND-Coping Scale, so that parametric analyses were valid, and to make it simpler for patients to complete and clinicians to score., Methods: After a new qualitative analysis of 26 patients with ALS/MND, the draft Coping Index-ALS (CI-ALS) was administered to 465 additional patients, alongside COPE-60, General Perceived Self Efficacy scale, and WHOQOL-BREF. Validity of the CI-ALS was assessed using the Rasch model. External validity was checked against comparator measures., Results: Thirteen centres contributed 465 patients, mean age 64.9 years (SD 10.8), mean disease duration 28.4 months (SD 37.5). The CI-ALS-Self and CI-ALS-Others both satisfied Rasch model expectations and showed invariance across age, gender, marital status and type of onset. Expected correlations were observed with comparator scales. A nomogram is available to convert the raw scores to interval level measures suitable for parametric analysis., Conclusions: Coping abilities in ALS/MND can now be measured using a simple 21 item self-report measure, offering two subscales with a focus of 'coping by self ' and 'coping with others'. This allows clinicians to identify individuals with poor coping and facilitates research on interventions that may improve coping skills., (Copyright © 2020. Published by Elsevier B.V.)

Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.

Background: Peritoneal dialysis-associated peritonitis can uncommonly be caused by fungal infections. When they do present, they are associated with significant mortality and morbidity. We describe a case where a sample of peritoneal dialysate fluid grew Rhodotorula muciliginosa, a yeast organism present in the normal environment which has previously been reported as rarely causing peritonitis. We believe this is the first case where the Rhodotorula spp. and its origin has been identified., Case Presentation: A 20 year old male grew Rhodotorula muciliginosa from his peritoneal dialysis fluid on three separate occasions when a fluid sample was sent following a disconnection and subsequent set change. He was not systemically unwell and his peritoneal dialysate was clear. As Rhodotorula spp. is exceedingly difficult to treat our patient had his Tenchkoff catheter removed. Subsequent samples of soil and sand from his bearded dragon and Chilean tarantula cases, kept in his bedroom where dialysis occurred, were tested. The tarantula sand was identified as the source of the Rhodotorula spp. Of note, Candida was isolated from sand from the bearded dragon case. Once his Tenchkoff was removed he was treated with an intravenous course of antifungal therapy. He has since had a new Tenchkoff catheter inserted and recommenced PD following education around pets and hygiene., Conclusions: In this era where people are keeping increasingly rare and unusual wildlife in their homes, this case highlights the need for clinician and nursing staff awareness of a patient's home environment and hobbies when they are undergoing peritoneal dialysis. Sand from our patient's tarantula case grew the colonising organism but interestingly soil from his bearded dragon case also isolated candida. This can also cause difficult to treat peritonitis.

Background: IgA nephropathy (IgAN) is the commonest glomerulonephritis worldwide. Its prevalence is difficult to estimate, as people with mild disease do not commonly receive a biopsy diagnosis. We aimed to generate an IgA nephropathy genetic risk score (IgAN-GRS) and estimate the proportion of people with hematuria who had IgAN in the UK Biobank (UKBB)., Methods: We calculated an IgAN-GRS using 14 single-nucleotide polymorphisms (SNPs) drawn from the largest European Genome-Wide Association Study (GWAS) and validated the IgAN-GRS in 464 biopsy-proven IgAN European cases from the UK Glomerulonephritis DNA Bank (UKGDB) and in 379,767 Europeans in the UKBB. We used the mean of IgAN-GRS to calculate the proportion of potential IgAN in 14,181 with hematuria and other nonspecific renal phenotypes from 379,767 Europeans in the UKBB., Results: The IgAN-GRS was higher in the IgAN cohort (4.30; 95% confidence interval [95% CI: 4.23-4.38) than in controls (3.98; 3.97-3.98; P  < 0.0001). The mean GRS in UKBB participants with hematuria ( n  = 12,858) was higher (4.04; 4.02-4.06) than UKBB controls (3.98; 3.97-3.98; P  < 0.0001) and higher in those with hematuria, hypertension, and microalbuminuria ( n  = 1323) (4.07; 4.02-4.13) versus (3.98; 3.97-3.98; P  = 0.0003). Using the difference in these means, we estimated that IgAN accounted for 19% of noncancer hematuria and 28% with hematuria, hypertension, and microalbuminuria in UKBB., Conclusions: We used an IgAN-GRS to estimate the prevalence of IgAN contributing to common phenotypes that are not always biopsied. The noninvasive use of polygenic risk in this setting may have further utility to identify likely etiology of nonspecific renal phenotypes in large population cohorts., (Crown Copyright © 2020 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

Objectives: The World Health Organization Quality of Life-BREF Scale (WHOQOL-BREF) is a generic QOL measure with four domains covering Physical, Psychological, Social and Environment. Providing the opportunity to contrast QoL with other conditions, or with population norms, the current study had three aims: 1) can the established domains of the WHOQOL-BREF be validated within a large ALS/MND population; 2) can a total score be validated and 3) can they provide interval level measurement? Methods: Data were obtained from the Trajectories of Outcomes in Neurological Conditions study. Internal construct validity was determined by fit of the data to the Rasch measurement model. Results: 636 participants with ALS/MND were included. All domains, except the Social domain, showed satisfactory fit to the Rasch model. All were unidimensional, and showed no Differential Item Functioning by age, gender, or onset type. Finally, a total score was validated from a bi-factor perspective. Conclusions: The WHOQOL-BREF is valid for use in populations with ALS/MND and can be analyzed to yield interval level measurement: It offers a range of domains that reflect QOL, which can be used for parametric analysis and for comparison with other conditions or general populations, two advantages for its inclusion as a trial outcome measure and for observational studies.

Monogenic diabetes and hyperinsulinism are genetically heterogeneous disorders. The determination of the genetic etiology defines the diagnostic subtype, predicts prognosis, and importantly can guide clinical management. This chapter focuses on the processes and methodologies utilized in the diagnostic testing for monogenic diabetes and congenital hyperinsulinism (i.e., Sanger sequencing and targeted next-generation sequencing).

Introduction: Our aim was to question the usefulness of a three-phase bone scan in the evaluation of pain in the knee region after TKR. Our hypothesis was that an abnormal investigation had a poor association with the presence of infection or loosening, and did not provide any additional diagnostic information above that already available through other standard investigations., Methods: A retrospective study over a 24-month period was performed comprising 118 patients investigated with a TPBS. Investigations were summarised and analysed, and were classified as entirely normal, possibly abnormal, and definitely abnormal., Results: Thirty-three per cent (39/118) of TPBSs were reported as being entirely normal, 59% (69/118) as possibly abnormal, and 8% (10/118) as definitely abnormal. During the 24-month study period, 131 revision TKR procedures were performed at our institution; 9% (12/131) were investigated with TPBS and 91% (119/131) were not. No patient with an entirely normal pre-operative TPBS underwent revision TKR surgery. Eighty-five per cent (67/79) with an abnormal TPBS were managed conservatively. In our series, a TPBS had a positive predictive value of 2.53%, a negative predictive value of 100%, with an overall accuracy of 34.75% with 100% sensitivity (97.5% one-sided confidence interval 0-24.71%), and 33.62% specificity (95% confidence interval 53.29-72.37%), in the diagnosis of infection, or loosening with concurrent infection in determining the indication for revision surgery., Conclusion: A TPBS should only be considered following clinical evaluation, serological investigation, diagnostic imaging, and microbiological analysis of fluid obtained from arthrocentesis by a specialist revision arthroplasty surgeon. A TPBS may be useful in the situation where abnormal serology is present, but where repeated joint aspirations samples are inconclusive.

Objectives: Spasticity is a common and disabling feature of amyotrophic lateral sclerosis (ALS). There are currently no validated ALS-specific measures of spasticity. The aim of this study was to develop and use a self-report outcome measure for spasticity in ALS., Methods: Following semi-structured interviews with 11 ALS patients, a draft scale was administered across ALS clinics in the UK. Internal validity of the scale was examined using the Rasch model. The numerical rating scale (NRS) for spasticity and Leeds Spasticity scale (LSS) were co-administered. The final scale was used in a path model of spasticity and quality of life., Results: A total of 465 patients (mean age 64.7 years (SD 10), 59% male) with ALS participated. Spasticity was reported by 80% of subjects. A pool of 71 items representing main themes of physical symptoms, negative impact and modifying factors was subject to an iterative process of item reduction by Rasch analysis resulting in a 20-item scale-the Spasticity Index for ALS (SI-ALS)-which was unidimensional and free from differential item functioning. Moderate correlations were found with LSS and NRS-spasticity. Incorporating the latent estimate of spasticity into a path model, greater spasticity reduced quality of life and motor function; higher motor function was associated with better quality of life., Conclusions: The SI-ALS is a disease-specific self-report scale, which provides a robust interval-level measure of spasticity in ALS. Spasticity has a substantial impact on quality of life in ALS., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The aim of this study was to assess the benefit of a Technetium-99M (HDP) 3-phase bone scan (TPBS) as an additional diagnostic test in the evaluation of pain in the hip region following cemented total hip replacement (THR) surgery., Methods: A retrospective study over a 24-month period was performed comprising 100 patients investigated with a TPBS. Investigations were summarised and analysed, and were classified as entirely normal, possibly abnormal, and definitely abnormal., Results: 45% (45) of TPBSs were reported as being entirely normal, 50% (50) as possibly abnormal, and 5% (5) as definitely abnormal. During the 24-month study period 230 revision THR procedures were performed at our institution; 10% (24) were investigated with TPBS and 90% (206) were not. 29% (7/24) of patients investigated with a TPBS that subsequently underwent revision THR surgery had an entirely normal preoperative TPBS. 84% (38) with an abnormal TPBS were managed conservatively. A TPBS had a sensitivity of 29% (95% confidence interval (CI), 13%-51%) and a specificity of 50% (95% CI, 38%-62%) in the detection of infection, or loosening with concurrent infection., Conclusion: A TPBS should only be considered following clinical evaluation, serological investigation, diagnostic imaging and microbiological analysis of fluid obtained from arthrocentesis by a specialist revision arthroplasty surgeon. A TPBS may be useful in the situation where abnormal serology is present, but where repeated joint aspirations samples are inconclusive.

Objectives: To determine the cost-effectiveness of natriuretic peptide (NP) testing and specialist outreach in patients with acute heart failure (AHF) residing off the cardiology ward., Methods: We used a Markov model to estimate costs and quality-adjusted life-years (QALYs) for patients presenting to hospital with suspected AHF. We examined diagnostic workup with and without the NP test in suspected new cases, and we examined the impact of specialist heart failure outreach in all suspected cases. Inputs for the model were derived from systematic reviews, the UK national heart failure audit, randomized controlled trials, expert consensus from a National Institute for Health and Care Excellence guideline development group, and a national online survey. The main benefit from specialist care (cardiology ward and specialist outreach) was the increased likelihood of discharge on disease-modifying drugs for people with left ventricular systolic dysfunction, which improve mortality and reduce re-admissions due to worsened heart failure (associated with lower utility). Costs included diagnostic investigations, admissions, pharmacological therapy, and follow-up heart failure care., Results: NP testing and specialist outreach are both higher cost, higher QALY, cost-effective strategies (incremental cost-effectiveness ratios of £11,656 and £2,883 per QALY gained, respectively). Combining NP and specialist outreach is the most cost-effective strategy. This result was robust to both univariate deterministic and probabilistic sensitivity analyses., Conclusions: NP testing for the diagnostic workup of new suspected AHF is cost-effective. The use of specialist heart failure outreach for inpatients with AHF residing off the cardiology ward is cost-effective. Both interventions will help improve outcomes for this high-risk group., (Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: Mutations in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events., Design and Methods: Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP -region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments., Results: Nine European-origin, unrelated c.805&#95;825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the 'English founder', with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9-113 generations, equivalent to 225-2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability., Conclusions: The c.805&#95;825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein-protein interactions and AIP protein stability., (© 2017 The authors.)

A boy aged 7 years presented with his parents to the emergency department (ED). He had a known diagnosis of paroxysmal supraventricular tachycardia (SVT) and was under the care of paediatricians. He had been suffering episodes of palpitations and chest pain for over a year and had been prescribed atenolol 25 mg ON, though the side effects meant he had not taken it for a month prior to presentation. He had 2 previous confirmed episodes of SVT, one that reverted with Valsalva manoeuvres, and the other with intravenous adenosine. In the ED, an ECG was recorded showing SVT at 180 bpm. Aside from his tachycardia, he was haemodynamically stable. The postural modification of the Valsalva technique was performed within 5 min of arrival, with reversion to sinus rhythm occurring during the leg-lift phase on the first attempt. After 30 min of observation, the child remained stable and was discharged home., Competing Interests: Competing interests: None declared., (2017 BMJ Publishing Group Ltd.)

Objective: To test the feasibility of running a randomised controlled trial of a preconsultation web-based intervention (Presenting Asking Checking Expressing (PACE-D)) to improve the quality of care and clinical outcomes in patients with diabetes., Design and Setting: A feasibility study (with randomisation) conducted at outpatient diabetes clinics at two secondary care hospitals in Devon, UK., Participants: People with diabetes (type 1 and type 2) attending secondary care general diabetes outpatient clinics., Intervention: The PACE-D, a web-based tool adapted for patients with diabetes to use before their consultation to generate an agenda of topics to discuss with their diabetologist., Outcomes: The percentage of eligible patients who were recruited and the percentage of participants for whom routine glycosylated haemoglobin (HbA1c) data (the putative primary outcome) could be extracted from medical notes and who completed secondary outcome assessments via questionnaire at follow-up were reported., Results: In contrast with the planned recruitment of 120 participants, only 71 participants were randomised during the 7-month recruitment period. This comprised 18.7% (95% CI 14.9% to 23.0%) of those who were eligible. Mean (SD) age of the participants was 56.5 (12.4) years and 66.2% had type 1 diabetes. Thirty-eight patients were randomised to the intervention arm and 33 to the control arm. HbA1c data were available for only 73% (95% CI 61% to 83%) of participants at the 6 months follow-up. The questionnaire-based data were collected for 66% (95% CI 54% to 77%) of the participants at 6 months follow-up. Participants reported that the PACE-D tool was easy to use., Conclusions: A randomised controlled trial of the preconsultation web-based intervention as set out in our current protocol is not feasible without significant modification to improve recruitment and follow-up of participants. The study also provides insights into the feasibility and challenges of conducting complex intervention trials in everyday clinical practice., Trial Registration: ISRCTN75070242., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization., Competing Interests: The authors declare no competing financial interests.

Failure to clear oral secretions can be debilitating for patients with amyotrophic lateral sclerosis (ALS), but the treatment of this symptom is poorly defined and there is no consensus on best practice. The objective of this study was to identify the treatments that are commonly prescribed, and to describe how experienced clinicians manage a patient with treatment resistant symptoms. Twenty-three clinicians were approached, of which 19 from 16 centres across the UK provided case report forms for a total of 119 ALS patients identified as having problematic oral secretions. The use of five anticholinergics, salivary gland botulinum toxin injections, conservative management approaches and carbocisteine were reported. Of the 72 patients who were evaluated following the initiation of a first anticholinergic, 61% had symptomatic improvement. Only 19% of patients achieved symptomatic improvement with the use of an alternative anticholinergic when an initial anticholinergic achieved no symptomatic improvement. Problems with thick and thin secretions often coexisted, with 37% of patients receiving treatment for both types of problem. In conclusion, a variety of treatment options are employed by expert clinicians for problematic oral secretions in ALS patients. The variation in management highlights the need for further prospective research in this area.

To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases., Competing Interests: The authors declare no competing financial interests.

Background: Peripheral venous cannulation is an everyday practice in hospitals, which many adults find painful. However, anaesthesia for cannulation is usually only offered to children. Inadequate pain relief is not only unpleasant for patients but may cause anxiety about further treatment and deter patients from seeking medical care in the future. The aim of this study is to discover the most effective local anaesthetic for adult peripheral venous cannulation and to find out how the pain of local anaesthetic application compares with that of unattenuated cannulation., Methods: These aims are addressed through a systematic review, network meta-analysis and random-effects meta-analysis. Searching covered 12 databases including MEDLINE and EMBASE from 1990 to August 2015. The main included study design was RCTs. The primary outcome measure is self-reported pain, measured on a 100 mm visual analogue scale., Results: The systematic review found 37 includable studies, 27 of which were suitable for network meta-analysis and two for random-effects meta-analysis. The results of the network meta-analysis indicate that none of the 17 anaesthetic considered had a very high probability of being the most effective when compared to each other; 2 % lidocaine had the highest probability (44 %). When the anaesthetics were compared to no treatment, the network meta-analysis showed that again 2 % lidocaine was estimated to be the most effective (mean difference -25.42 (95 % CI -32.25, -18.57). Other members of the 'caine' family were also estimated to be more effective than no treatment as were Ametop ® , EMLA ® and Rapydan ® patch. The meta-analysis compared the pain of anaesthetic application with the unattenuated pain of cannulation. This found that all applications of local anaesthetic were less painful than cannulation without local anaesthetic. In particular a 1 % lidocaine injection was estimated to be -12.97 (95 % CI -15.71, -10.24) points (100 mm VAS) less painful than unattenuated cannulation., Conclusions: The pain of peripheral venous cannulation in adults can be successfully treated. The pain of application of any local anaesthetic is less than that of unattenuated cannulation. Local anaesthetic prior to cannulation should become normal practice and a marker of high quality care., Protocol Registration: The protocol for the larger study was registered with PROSPERO no. CRD42012002093 .

Background: Restrictive eating disorders in young people are increasingly requiring admission to the hospital and can be a challenge to manage on acute general paediatric wards., Methods: We have developed a joint working model with Child and Adolescent Mental Health services (CAMHS) using short, structured, supported feeding admissions to supplement outpatient treatment in high risk or 'stuck' cases., Results: We have successfully managed the majority of young people in the community avoiding lengthy, expensive, specialist CAMHS eating disorder inpatient unit admissions (tier 4). Local ward admissions are easier to manage and the attitudes of nursing and medical staff towards these young people have changed., Discussion: Joint working between paediatric and CAMHS teams enables shorter, more manageable local ward admissions, reducing the need for tier-4 units., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival., Objectives: To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation., Methods: Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association's electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time-state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death., Results: Eighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY., Limitations: For included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled., Future Work: High-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome., Conclusion: Only a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000-30,000 per QALY., Study Registration: This study is registered as PROSPERO CRD42014013189., Funding: The National Institute for Health Research Health Technology Assessment programme.

This painful ulcer, which had signs of biofilm, was covered in necrotic tissue. Octenilin Wound Gel was used to soften the necrosis in preparation for sharp debridement. Three weeks later, the devitalised tissue had been completely removed, while there was a 50% reduction in wound size at week 5.

This necrotic ulcer was managed with sharp debridement, octenilin Wound Irrigation Solution and Wound Gel, plus a non-adherent dressing. The significant oedema in the lower limb was controlled with reduced compression. The wound improved steadily over time, healing on week 16.

This painful and malodorous ulcer was covered with 40% necrotic tissue. Combined use of octenilin Wound gel and Wound Irrigation Solution gently debrided the necrotic tissue, and helped reduce the pain and malodour. Within 6 weeks, the wound was covered with granulation tissue.

Background and Aims: Nephrotoxicity is a rare idiosyncratic reaction to 5-aminosalicylate (5-ASA) therapies. The aims of this study were to describe the clinical features of this complication and identify clinically useful genetic markers so that these drugs can be avoided or so that monitoring can be intensified in high-risk patients., Methods: Inflammatory bowel disease patients were recruited from 89 sites around the world. Inclusion criteria included normal renal function prior to commencing 5-ASA, ≥50% rise in creatinine any time after starting 5-ASA, and physician opinion implicating 5-ASA strong enough to justify drug withdrawal. An adjudication panel identified definite and probable cases from structured case report forms. A genome-wide association study was then undertaken with these cases and 4109 disease controls., Results: After adjudication, 151 cases of 5-ASA-induced nephrotoxicity were identified. Sixty-eight percent of cases were males, with nephrotoxicity occurring at a median age of 39.4 years (range 6-79 years). The median time for development of renal injury after commencing 5-ASA was 3.0 years (95% confidence interval [CI] 2.3-3.7). Only 30% of cases recovered completely after drug withdrawal, with 15 patients requiring permanent renal replacement therapy. A genome-wide association study identified a suggestive association in the HLA region (p = 1×10(-7)) with 5-ASA-induced nephrotoxicity. A sub-group analysis of patients who had a renal biopsy demonstrating interstitial nephritis (n = 55) significantly strengthened this association (p = 4×10(-9), odds ratio 3.1)., Conclusions: This is the largest and most detailed study of 5-ASA-induced nephrotoxicity to date. It highlights the morbidity associated with this condition and identifies for the first time a significant genetic predisposition to drug-induced renal injury., (Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Blood insulin and C-peptide are key investigations in the differential diagnosis of hypoglycaemia. Analogues of insulin have modified primary-sequences compared to native human insulin, as such may not cross react with insulin assays. This has important implications in detecting surreptitious or malicious insulin administration. The aim of this study is to assess the cross-reactivity of all insulins currently listed in the British National Formulary (BNF65, 2013) in clinical insulin assays currently used in UK clinical laboratories., Design and Methods: Sample sets were prepared for all 15 exogenous insulin classes listed in the BNF, at concentrations of 1000 pmol/L and 300 pmol/L, using pooled human serum. Samples were sent blinded to 5 participating analytical laboratories to cover analysis on the 10 major clinical insulin assays used in the UK., Results: The ability of insulin assays to detect exogenous insulin preparations was highly variable and ranged from 0% to >140% for a single exogenous insulin. Four assays were highly specific for the human insulin sequence and had no cross-reactivity with any synthetic analogue insulin. Two detected all insulin types (human sequence, animal and synthetic analogue), with the remaining having variable cross-reactivity., Conclusion: The cross-reactivity of the 15 exogenous insulin preparations is highly variable in the assays used in clinical laboratories around the UK. It is important that laboratories and clinicians are aware of the limitations of their local assays to avoid missing the important diagnosis of hypoglycaemia secondary to excessive exogenous insulin. Where necessary, samples should be referred to specialist centres for insulin analysis and ideally by a validated and fully-quantitative mass spectrometry-based method., (Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Unlabelled: A patient of Cushing's disease (CD) characterized by a large tumor and only subtle symptoms of hormonal hypersecretion was examined. The patient had a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene. A 50-year-old male presenting with headache was diagnosed with a large pituitary tumor by magnetic resonance imaging (MRI). His visual fields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnight dexamethasone suppression test was performed revealing inadequate suppression of plasma cortisol (419 nmol/l). Owing to tumor growth and visual field impairment, he underwent transsphenoidal surgery and developed hypocortisolemia. The pathology specimen revealed a sparsely granulated corticotrope adenoma. Postoperative MRI showed a large tumor remnant. The patient developed skin hyperpigmentation and a synacthen test demonstrated high basal and stimulated cortisol levels; an overnight dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma ACTH levels (135 ng/l). A transcranial operation was performed followed by radiotherapy. Two months after radiotherapy, he developed secondary adrenocortical failure. Genetic testing revealed an AIP variant of unknown significance (p.R16H) without loss of the normal AIP allele in the tumor. A literature review showed ten CD patients with AIP gene variants, of whom five (including our case) were p.R16H. CD is occasionally dominated by pituitary tumor growth rather than symptoms of hypersecretion. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD. Future studies are needed to assess whether the reported AIP gene variant is more than just coincidental., Learning Points: CD is occasionally dominated by pituitary tumor growth rather than symptoms of hypersecretion.Resolution of both tumor remnant and hormonal hypersecretion may occur within 2 months after postoperative radiotherapy.The particular AIP gene variant identified in our patient is shared by four other reported cases of CD.

Background: The aim of treatment of frozen shoulder is to regain a painless and functional shoulder range of shoulder motion. In this study we evaluated the results of using the arthroscopic technique for the release of the shoulder joint capsule in patients with a diagnosis of frozen shoulder., Material and Methods: The study included 40 patients with frozen shoulder. They were operated upon with the use of electrocautery for the release of the shoulder joint capsule. The group consisted of 29 women and 11 men with a mean age of 48.2 years (range 38-62)., Results: Preoperatively, the mean Constant and Murly shoulder score was 36.35 (range 21-51). At the end of the follow up period, the mean score was 85.8 (range 62 to 98). The difference between the means of pre- and postoperative total score was statistically significant (t =10.85 and p=0.0001). 22 patients (55%) had excellent results, 14 patients (35%) had good results, 4 patients (10%) had fair results and none had poor results. The 4 cases with fair results were all female, all had insulin-dependent diabetes mellitus and were > 50 years old., Conclusions: 1. Arthroscopic capsular release is an effective and safe method for the treatment of refractory frozen shoulder. 2. It achieves dramatic pain and motion improvement post-operatively, allowing very early postoperative rehabilitation.

Background: Calcaneal fractures are the most common fractures of the tarsal bones. The majority of these fractures are produced by axial force like a fall from a height. Controversy still exists on the best line of treatment. This study is to evaluate the results of trans-osseous limited lateral approach as a minimally invasive surgical treatment of the displaced intra-articular calcaneal fractures., Material and Methods: The study included forty two patients (46 feet) with displaced intra-articular calcaneal fractures admitted to El-Hadra University Hospital. They were treated by trans-osseous open reduction of subtalar joint and internal fixation by k-wires consuming the trans-osseous limited lateral approach. Out of 42 patients, 36 pateints (85.7%) were males., Results: Using calcaneal fracture scoring system, the mean score was 67.55+17.35. Satisfactory results were found in 26 patients (61.9%), while 16 patients (38.1%) had unsatisfactory results. There was significant relationship between classification of the fracture and the final results (the more the grade of the fracture, the worse the final score) (x 2 =5.914, p=0.05). The value of calcaneal angles were significantly improved after surgery including bohler angle (p=0.0001), gissane angle (p=0.0001), calcaneal pitch angle (p=0.001) and calcaneofibular space (p=0.0021)., Conclusions: 1. Trans-osseous limited lateral approach is an effective method for management of intra articular calcaneal fractures. 2. Anatomical reduction for intra articular calcaneal fractures is essential. 3. Functional outcome of intra articular calcaneal fractures depends upon the initial damage of the articular cartilage. 4. There is a need for multi-center prospective randomized study for accurate assessment of the results of operative management of intra articular calcaneal fractures involving pre and post-operative CT for assessment of reduction and using a rational scoring system and a long period of follow up.

Patients with attacks of re-entrant supraventricular tachycardia (SVT) frequently present to the emergency department (ED). The Valsalva manoeuvre (VM) is the most effective and safe vagal manoeuvre and advocated as the first-line treatment in stable patients but has a relatively low cardioversion success rate. Improving its efficacy would reduce patients' exposure to the side effects and complications of second-line treatments and has other potential benefits. We describe a modification to the VM, which is currently being studied, and present the case of a 23-year-old patient who was successfully treated with this modified VM after a previous near-fatal complication of direct current (DC) cardioversion., (2014 BMJ Publishing Group Ltd.)

Background: Williams syndrome (WS) is a rare neurodevelopmental disorder arising from a hemizygotic deletion of approximately 27 genes on chromosome 7, at locus 7q11.23. WS is characterised by an uneven cognitive profile, with serious deficits in visuospatial tasks in comparison to relatively proficient performance in some other cognitive domains such as language and face processing. Individuals with partial genetic deletions within the WS critical region (WSCR) have provided insights into the contribution of specific genes to this complex phenotype. However, the combinatorial effects of different genes remain elusive., Methods: WE REPORT ON VISUOSPATIAL COGNITION IN TWO INDIVIDUALS WITH CONTRASTING PARTIAL DELETIONS IN THE WSCR: one female (HR), aged 11 years 9 months, with haploinsufficiency for 24 of the WS genes (up to GTF2IRD1), and one male (JB), aged 14 years 2 months, with the three most telomeric genes within the WSCR deleted, or partially deleted., Results: Our in-depth phenotyping of the visuospatial domain from table-top psychometric, and small- and large-scale experimental tasks reveal a profile in HR in line with typically developing controls, albeit with some atypical features. These data are contrasted with patient JB's atypical profile of strengths and weaknesses across the visuospatial domain, as well as with more substantial visuospatial deficits in individuals with the full WS deletion., Conclusions: Our findings point to the contribution of specific genes to spatial processing difficulties associated with WS, highlighting the multifaceted nature of spatial cognition and the divergent effects of genetic deletions within the WSCR on different components of visuospatial ability. The importance of general transcription factors at the telomeric end of the WSCR, and their combinatorial effects on the WS visuospatial phenotype are also discussed.

Since the original description of the effectiveness of β-blockers in lowering the portal pressure and therefore the risk of variceal bleeding, more than 500 articles in the English literature on the use of non selective β-blockers (NSBB) in cirrhosis have been published. The use of NSBB in pre-primary prophylaxis of variceal bleeding is currently not indicated. In primary prophylaxis, patients with high risk small varices or large/medium varices should receive primary prophylaxis either with NSBB or with endoscopic band ligation if there are contraindications to NSBB. For secondary prophylaxis the current recommendation is to receive a combination of NSBB and endoscopic variceal ligation. In addition to lowering portal pressure, NSBB can also reduce bacterial translocation, potentially exerting multiple beneficial effects which go beyond the reduction of bleeding risk. Carvedilol is a NSBB with intrinsic anti-α(1)-adrenergic activity, possibly more effective than propranolol in lowering portal hypertension. A potential harmful effect of propranolol in patients with cirrhosis with refractory ascites deserves further confirmation. NSBB remain the cornerstone of therapy in cirrhotic patients with portal hypertension.